Compositions, systems, and methods for immiscible fluid discrete volume manipulation

• US 9,152,150 B1
• Filed: 02/22/2008
• Issued: 10/06/2015
• Est. Priority Date: 02/22/2007
• Status: Active Grant

• Current Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Original Assignee: Applied Biosystems LLC (Thermo Fisher Scientific Incorporated)
• Inventors: Lee, Linda G., Oldham, Mark F., Woo, Sam L., Cox, David M., Reel, Richard T., Johnson, Ben F., Ma, Peter N., Letho, Dennis
• Primary Examiner(s): MURPHY, KEVIN F
• Application Number:
  US12/036,037
• Time in Patent Office: 2,783 Days
• Field of Search: 137/114, 137/896, 137/897, 137/88, 422/82, 436/53
• US Class Current: 1/1
• CPC Class Codes: B01F 23/4105 Methods of emulsifying
• CPC Class Codes: B01F 23/411 using electrical or magnetic fields, heat or vibrations
• CPC Class Codes: B01F 23/4145 Emulsions of oils, e.g. fuel, and water
• CPC Class Codes: B01F 25/314 wherein additional components are introduced at the circumference of the conduit
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01F 33/3022 the components being formed by independent droplets which are alternated, the mixing of the components being achieved by diffusion between droplets
• CPC Class Codes: B01F 33/3031 using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
• CPC Class Codes: B01L 2200/06 Fluid handling related problems
• CPC Class Codes: B01L 2200/0605 Metering of fluids
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0481 squeezing of channels or chambers
• CPC Class Codes: B01L 2400/0666 Solenoid valves
• CPC Class Codes: B01L 3/0265 using valves to interrupt or meter fluid flow, e.g. using solenoids or metering valves
• CPC Class Codes: B01L 3/502769 characterised by multiphase flow arrangements
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: G01N 1/38 Diluting, dispersing or mixing samples
• CPC Class Codes: G01N 2001/386 Other diluting or mixing processes
• CPC Class Codes: G01N 2021/6439 with indicators, stains, dyes, tags, labels, marks
• CPC Class Codes: G01N 21/6428 : Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 35/08 : using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: G05D 11/131 : by measuring the values related to the quantity of the individual components G05D11/139 takes precedence
• CPC Class Codes: G05D 7/0694 : by action on throttling means or flow sources of very small size, e.g. microfluidics microvalves F16K99/0001; microstructural devices per se B81B

Abstract

Systems and methods of manipulating discrete volumes of a first fluid in a second fluid are provided. In some embodiments, discrete volumes can be formed in a conduit. In other embodiments, addition fluid can be added to a discrete volume in a first conduit by injecting the addition fluid at a relatively higher pressure. In some embodiments, discrete volumes that normally would not coalesce can be manipulated to be merged together.

Claims

1. A system comprising:

a first conduit;

a composition in the first conduit, the composition comprising an oil and discrete volumes of an aqueous fluid in the oil, the oil and the aqueous fluid being immiscible with one another and the discrete volumes being spaced apart from one another;

a second conduit in fluid communication with the first conduit, at a junction, wherein the second conduit contains an oil;

a valve disposed along the second conduit wherein the valve is configured to be actuated for a period between 0.1 milliseconds to about 10 milliseconds, a blue LED detector;

a volume detection sensor configured to the detect the length of each discrete volume of aqueous fluid; and

a control system associated with the valve and configured to;

open the valve when one of the discrete volumes is present at the junction,

determine a flow rate of the discrete volumes of aqueous fluid, and

determine a pressure and volume of oil to inject into the discrete volume of aqueous fluid,

wherein the system is configured to segment a discrete volume of aqueous fluid by opening the valve and injecting oil located in the second conduit into the first conduit.

2. The system of claim 1, wherein the valve comprises a solenoid valve.

3. The system of claim 1, further comprising a pump associated with the valve, wherein the control system is configured to actuate the valve and power the pump.

4. The system of claim 3, wherein the circuitry is programmed to actuate the valve, from a non-actuated position, one or more times within a 100 millisecond period, upon a triggering event.

5. The system of claim 4, wherein the triggering event comprises a detection of one of the discrete volumes at or near the junction.

6. A system comprising:

a first conduit;

a composition in the first conduit, the composition comprising an oil and discrete volumes of an aqueous fluid in the oil, the oil and the aqueous fluid being immiscible with one another and the discrete volumes being spaced apart from one another;

a second conduit in fluid communication with the first conduit, at a junction, wherein the second conduit contains an oil;

a valve disposed along the second conduit,

a blue LED detector; and

a pump configured to pump a liquid through the second conduit and configured to provide multiple bursts of pressure within a 100 millisecond period,

a volume detection sensor configured to the detect the length of each discrete volume of aqueous fluid; and

a control system associated with the valve and configured to;

open the valve when one of the discrete volumes is present at the junction,

determine a flow rate of the discrete volumes of aqueous fluid, and

determine a pressure and volume of oil to inject into the discrete volume of aqueous fluid,

wherein the system is configured to segment a droplet by opening the valve and injecting oil located in the second conduit into the first conduit.

7. A system comprising:

a first conduit;

an oil in the first conduit;

a second conduit in fluid communication with the first conduit, at a junction;

an aqueous fluid in the second conduit, the oil and the aqueous fluid being immiscible with one another;

a valve disposed along the second conduit a blue LED detector; and

a volume detection sensor configured to the detect the length of each discrete volume of aqueous fluid

a fluid movement system configured to;

open the valve and force portions of the aqueous fluid from the second conduit into the first conduit to form discrete volumes of the aqueous fluid spaced apart from one another, in the oil,

determine a flow rate of the discrete volumes of aqueous fluid, and

determine a pressure and volume of oil to inject into the discrete volume of aqueous fluid,

wherein the system is configured to segment a droplet by opening the valve and introducing aqueous fluid located in the second conduit into the first conduit,

wherein the flow of oil in the first conduit is configured to segment the aqueous fluid entering the first conduit.

8. The system of claim 7, wherein the fluid movement system comprises one or more pumps, at least one of the one or more pumps is configured to pump the aqueous fluid through the second conduit at a predetermined rate, and the valve is configured to be actuated for a period of time based on the rate to provide discrete volumes of a pre-selected volume.